This is a proposal requesting continuing support for integrative predoctoral training of physician-scientists attaining combined M.D. and Ph.D. degrees through the University of Washington Medical Scientist Training Program (UW MSTP). The overall goal is to identify, develop, recruit, train, inspire, and mentor the next generation o a highly well-qualified and broadly diverse group of physician-scientists, reflecting the composition of our nation, who will be equipped to bridge the gap between the basic sciences and its translational application and who will be prepared to help usher in exciting and revolutionary advances in the understanding and treatment of known and emerging diseases. As the only MSTP representing a vast geographic swatch of the United States, our program is amongst the most longstanding of NIH-funded MSTPs yet continues to evolve under a new generation of program leadership alongside other innovative recently introduced changes. The program is currently intended to enroll 10 new trainees each year for a curriculum designed to be completed in 8 years, resulting in a steady-state of about 80 students. The program integrates medical and basic science training in which students participate in medical school and graduate school courses while also completing MSTP-specific coursework as well as tailored laboratory and clinical training, along with training in the ethical conduct of research, with approximately one-quarter of trainees instantly engaged in the basic sciences phase of medical school, one-half completing graduate coursework and dissertation research, and one-quarter completing medical school clinical clerkships. At any given time, 29 of the trainees will be supported by this grant, with the remainder of funding being provided by trainee NRSA or equivalent awards, other institutional training grants, mentor research awards, and scholarships or other institutional support. The Fred Hutchinson Cancer Research Center contributes a major component of faculty resources and training. Other participating institutions include Seattle Biomed, Seattle Children's Research Institute, and the Benaroya Research Institute. All biomedical and basic science research disciplines are represented. Major pan-institutional participating programs and departments include the Molecular and Cellular Biology Program, the Neurobiology and Behavior program, and Departments of Genome Sciences, Bioengineering, Global Health, Immunology, Pathology, Physiology and Biophysics, Pharmacology, and Biostatistics. The program is backed by enormous institutional support, and a core of 69 highly distinguished faculty selected from among a legion at participating institutions are devoted to mentoring trainees and administrating the program. Graduates of our program typically complete clinical residency and postdoctoral fellowship subspecialty training and assume leadership positions at prestigious academic medical centers and research institutions worldwide.